The Smc5/6 complex is required for dissolution of DNA-mediated sister chromatid linkages |
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| Authors: | Marcelino Bermúdez-López Audrey Ceschia Giacomo de Piccoli Neus Colomina Philippe Pasero Luis Aragón Jordi Torres-Rosell |
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| Institution: | 1.IRBLLEIDA, Department of Ciències Mèdiques Bàsiques, Facultat de Medicina, Universitat de Lleida, c/Montserrat Roig 2, 25008 Lleida, Spain, 2.Cell Cycle Group, MRC Clinical Sciences Centre, Imperial College London, Du Cane Road, London W12 0NN, UK and 3.Department of Genome Dynamics, Institute of Human Genetics, CNRS UPR 1142, Montpellier, France |
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| Abstract: | Mitotic chromosome segregation requires the removal of physical connections between sister chromatids. In addition to cohesin and topological entrapments, sister chromatid separation can be prevented by the presence of chromosome junctions or ongoing DNA replication. We will collectively refer to them as DNA-mediated linkages. Although this type of structures has been documented in different DNA replication and repair mutants, there is no known essential mechanism ensuring their timely removal before mitosis. Here, we show that the dissolution of these connections is an active process that requires the Smc5/6 complex, together with Mms21, its associated SUMO-ligase. Failure to remove DNA-mediated linkages causes gross chromosome missegregation in anaphase. Moreover, we show that Smc5/6 is capable to dissolve them in metaphase-arrested cells, thus restoring chromosome resolution and segregation. We propose that Smc5/6 has an essential role in the removal of DNA-mediated linkages to prevent chromosome missegregation and aneuploidy. |
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